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The race to develop even more effective obesity drugs is heating up. This week, Novo Nordisk announced that people taking its mega-dose version of semaglutide lost substantially more body weight than usual in a large-scale trial.
Novo Nordisk’s STEP UP trial involved more than 1,400 people with obesity, some of whom were randomized to receive a 7.2 milligram dose of semaglutide. People who stayed on this dose lost around 20% of their baseline weight over a 72 week period. The findings exceed the typical weight loss results seen with the existing semaglutide-based drugs Ozempic and Wegovy.
Semaglutide mimics the hormone GLP-1, which helps regulate our hunger and metabolism. It’s the active ingredient in type 2 diabetes drug Ozempic and the higher-dose obesity drug Wegovy. Since Wegovy’s FDA approval in 2021, Ozempic has often been prescribed off-label for weight loss. In large-scale, placebo-controlled trials of Wegovy, people have lost around 15% of their weight, well above the average weight loss seen with diet and exercise or with older obesity drugs.
The emergence of semaglutide has ushered in a new era of obesity treatment. And both Novo Nordisk and its competitors have made efforts to develop the next generation of these drugs. While Wegovy is already a higher-dose formulation of semaglutide (its maximum prescribed dose is 2.4 milligrams, compared to the maximum one milligram dose for Ozempic), the company is banking that the drug’s effectiveness hasn’t yet reached its ceiling.
The STEP UP trial included three groups: People who were either given a placebo, a Wegovy-sized 2.4 milligram dose of semaglutide, or a 7.2 milligram dose.
When looking at people who fully adhered to the medication schedule (a weekly injection under the skin), those on the 7.2 milligram dose lost an average 20.7% body weight after 72 weeks, compared to 17.5% lost body weight for the 2.4 milligram group, and 2.4% lost body weight for the placebo group. And even when including people who didn’t fully adhere, the higher-dose version still outperformed the original (18.7% lost body weight compared to 15.6%).
Just as importantly, the higher dose version of semaglutide appeared to be generally safe and tolerable. In the trial, the 7.2 milligram group experienced side effects that were comparable to the lower dose group, according to Novo Nordisk. GLP-1 drugs are known to cause gastrointestinal symptoms like diarrhea or vomiting, though these effects are often mild to moderate and tend to fade over time. Much more rarely, scientists have linked GLP-1 drugs to severe complications like gastroparesis (stomach paralysis).
“Results from STEP UP further strengthen the clinical profile of semaglutide for the treatment of obesity, in addition to the health benefits already established with Wegovy,” said Martin Holst Lange, executive vice president for Development at Novo Nordisk, in a statement from the company.
The company will also soon release the results of its STEP UP T2D trial, which tested a 7.2 milligram dose for people with obesity and type 2 diabetes. Assuming things go to plan, semaglutide is likely to have an extended shelf life as a top-tier obesity and diabetes treatment for Novo Nordisk, even with other companies fast approaching with their own drug candidates on the way. But even its highest-dose version is expected to face stiff competition.
In a head-to-head trial disclosed late last year, Eli Lilly’s existing drug tirzepatide (the active ingredient in diabetes medication Mounjaro and obesity treatment Zepbound) outperformed Wegovy, with an average 20.2% lost body weight compared to 13.7%. Other obesity drugs in development have also shown early, but promising results that might overshadow both tirzepatide and semaglutide.
Another consideration is cost. The current lower-dose formulations of semaglutide have been around for years at this point, and their high list prices (around $1,000 per month) have angered both the public and lawmakers. Just this week, the federal government announced that it would schedule both Ozempic and Wegovy for the next round of its recently debuted drug negotiation program under Medicare (any potential cuts would not come into effect until 2027, however). While a higher-dose of semaglutide may be more effective at treating obesity, it would likely also allow the company to continue selling its drug at a similar or even higher price than today’s versions.
The future of obesity treatment is looking bright, but it’s also going to be costly.
